title: Effect of glucagon-like peptide-1 on beta- and alpha-cell function in isolated islet and whole pancreas transplant recipients.
abstract: BACKGROUND
  Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced beta-cell secretory capacity indicates a low functional beta-cell mass.
  
  
  OBJECTIVE
  We sought to determine whether glucagon-like peptide-1 (GLP-1) enhanced glucose-dependent insulin secretion and glucagon suppression in islet recipients, and whether GLP-1 effects were dependent on functional beta-cell mass by simultaneously studying recipients of whole pancreas transplants.
  
  
  METHODS
  The study was performed in a clinical and translational research center.
  
  
  METHODS
  Five intraportal islet and six portally drained pancreas transplant recipients participated in the study.
  
  
  METHODS
  Subjects underwent glucose-potentiated arginine testing with GLP-1 (1.5 pmol . kg(-1) . min(-1)) or placebo infused on alternate randomized occasions, with 5 g arginine injected under basal and hyperglycemic clamp conditions.
  
  
  RESULTS
  Basal glucose was lower with increases in insulin and decreases in glucagon during GLP-1 vs. placebo in both groups. During the hyperglycemic clamp, a significantly greater glucose infusion rate was required with GLP-1 vs. placebo in both groups (P < 0.05), an effect more pronounced in the pancreas vs. islet group (P < 0.01). The increased glucose infusion rate was associated with significant increases in second-phase insulin secretion in both groups (P < 0.05) that also tended to be greater in the pancreas vs. islet group (P = 0.08), whereas glucagon was equivalently suppressed by the hyperglycemic clamp during GLP-1 and placebo infusions in both groups. The GLP-1-induced increase in second-phase insulin correlated with the beta-cell secretory capacity (P < 0.001). The proinsulin secretory ratio (PISR) during glucose-potentiated arginine was significantly greater with GLP-1 vs. placebo infusion in both groups (P < 0.05).
  
  
  CONCLUSIONS
  GLP-1 induced enhancement of glucose-dependent insulin secretion, but not glucagon suppression, in islet and pancreas transplant recipients, an effect dependent on the functional beta-cell mass that may be associated with depletion of mature beta-cell secretory granules.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 700 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149, USA. rickels@mail.med.upenn.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mueller
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D050416:Glucagon-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011384:Proinsulin / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011384:Proinsulin; D001120:Arginine